Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension

Endothelial nitric oxide synthase (eNOS), encoded by NOS3, is a potent regu lator of vasomotor tone and peripheral resistance. Congenic experiments ind icate that a chromosomal segment containing the rat eNOS gene contributes t o rat spontaneous hypertension (HT). A role for NOS3 in onset of essential hypertension (HT) is, however, controversial. We therefore decided to test NOS3 polymorphisms in a set of patients who have an accentuated ability to show an existing genetic association. The 112 HT subjects had two HT parent s and the normotensive (NT) subjects had two NT parents. All were Anglo-Cel tic whites. The two most promising polymorphisms, viz, a biallelic variable number of tandem repeats (VNTR) in intron 4 and an exon 7 variant that lea ds to an amino acid change (Glu298Asp), were genotyped by PCR (and BanII di gestion in the case of the latter). Frequency of the minor allele of the VN TR was 0.11 in the NT and 0.10 in the HT subjects (P = .9). For the exon 7 variant, Asp298 frequency was 0.30 and 0.32 in each respective group (P = . 6). Tracking was seen for the Asp298 allele with elevation in body mass ind ex (P = .034), and the minor allele of the VNTR with elevation in LDL (P = .007) and reduction in HDL (P = .048). In conclusion, we saw no association of NOS3 markers with HT in the population studied. However, possible genot ypic effects on plasma lipids and body mass index might warrant further stu dies, especially in view of possible associations with heart disease. Am J Hypertens 2000;13:994-998 (C) 2000 American Journal of Hypertension, Ltd.